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August 28, 2007

Epithelial-Cell Barrier Suppresses Oncogene Function

  • The tightly organized architecture of mammary epithelial cells acts as a restraint against the proliferation of cancer genes, according to University of Helsinki researchers. Their study also links the lack of a protein to the formation of a disorganized epithelial environment, which in turn enables oncogene activity.

    Experiments with fly models have shown that loss of epithelial organization can enhance the tumorigenic potential of oncogenes. These findings prompted the researchers to explore whether the reverse action—formation of epithelial organization—suppresses oncogene function.

    “We were amazed to find out that the formation of organized mammary epithelial architecture in three-dimensional organotypic cell culture correlated with complete loss of oncogenic activities of c-Myc cancer gene,” remarks Juha Klefstrom, Ph.D., research team leader.

    “We also asked how to dismantle the proliferation resistance of the epithelial organization,” continues Johanna Partanen, a graduate student in Klefstrom’s laboratory and lead author in the article.

    Previously, geneticists working with fly models identified an important group of genes, Par genes, that regulate the development of highly ordered epithelial cell organization. “The most interesting candidate for us was LKB1, the human homologue of Par4 protein, because this gene has strong connection to human epithelial disorders,” says Partanen.

    Dr. Klefstrom’s team found that epithelial cells missing the LKB1 protein are able to form only disorganized epithelial structures. This disorganized environment enables c-Myc oncogene to drive inappropriate cell proliferation.

    The work appears this week in the online edition of the Proceedings of the National Academy of Sciences.

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